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Biomedical subjects

Christian Hamm

Publications and source records attributed to Christian Hamm.

At least 19 recordsLinked to original sources

Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial.

CONTEXT: Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. OBJECTIVE: To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. DESIGN, SETTING, AND PATIENTS: This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. INTERVENTIONS: Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. MAIN OUTCOME MEASURES: The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. RESULTS: No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91). CONCLUSION: In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00091637.

Aged↗

Influence of sample type and storage conditions on soluble CD40 ligand assessment.

BACKGROUND: Several studies have consistently shown that soluble CD40 ligand (sCD40L) concentrations are increased in patients with acute coronary syndromes and can serve as a biomarker for risk stratification. However, few data are available on preanalytic conditions that impact sCD40L values. Thus, the aim of our prospective study was to evaluate the impact of sampling techniques and storage conditions on sCD40L concentrations. METHODS: We included a total of 30 patients with no, stable, or unstable coronary heart disease. Blood samples were collected in gel-filled tubes without additives, in EDTA-filled tubes, and in citrate-filled tubes and were kept at various storage conditions. RESULTS: Median (interquartile range) sCD40L values at baseline were higher in serum samples [5.29 (3.89-6.33) microg/L] than in either EDTA plasma [0.78 (0.39-1.12) microg/L; P <0.001] or citrate plasma [0.37 (0.22-0.51) microg/L; P <0.001]. Serum values increased with delayed processing [7.94 (5.97-9.62) microg/L after 1.5 h (P <0.001) vs baseline; 10.55 (7.58-11.55) microg/L after 3 h (P <0.001) vs baseline]. However, after centrifugation, sCD40L values remained stable for all 3 sample types. CONCLUSION: Plasma, but not serum, samples are appropriate for sCD40L measurements. In general, preanalytic conditions are critical in the assessment of sCD40L concentrations and thus should be carefully considered for future studies.

Biomarkers↗

[Biomarkers for the evaluation of valvular aortic stenosis].

Aortic valve diseases, namely aortic stenosis (AS) and aortic regurgitation (AR), are common in developed countries with AS being the most common valvular heart disease. Symptomatic status and echocardiography are the most important clinical parameters to confirm the diagnosis, to assess the severity and to monitor progression of AS. Aortic valve replacement (AVR) is indicated in symptomatic patients with severe AS, but in asymptomatic patients with severe AS there is an ongoing controversial discussion whether these patients should undergo AVR or should be treated conservatively. For patients with moderate AS, surgical treatment is generally not recommended, even though recent data suggest that the outcome of these patients is worse than commonly assumed.In several studies that included patients with valvular AS, an elevation of BNP and NT-proBNP serum concentrations related to disease severity has been reported (Figure 1). Consequently, in a longitudinal study it was found, that NT-proBNP concentrations decrease after successful surgical therapy but increase in conservatively treated patients with AS (Figure 2). These changes of NT-proBNP values over time were related to changes of the transvalvular pressure gradient (Figure 3). Furthermore, it has been demonstrated in clinical outcome studies that elevated NT-proBNP and BNP values, respectively, were associated with an unfavorable clinical course especially in patients who were treated conservatively (Figure 4).Thus, these results suggest that natriuretic peptides can be used as biomarkers for the diagnostic work-up of patients with AS and might be helpful to decide on the optimal timing of AVR (Table 1).

Aortic Valve↗

Acute success and persistence of bidirectional conduction block in the cavotricuspid isthmus one month post cryocatheter ablation of common atrial flutter.

INTRODUCTION: Cryoablation is successful in the treatment of common atrial flutter. Long-term clinical success is mainly dependent on persistence of bidirectional conduction block (BCB) in the inferior cavotricuspid isthmus (CTI). Only few data on persistence of BCB post cryoablation with the reported technique are available. This prospective study aimed to test efficacy of cryo energy and persistence of BCB in the CTI 1 month post cryoablation. METHODS: Cryoablation of the CTI was performed in 50 consecutive patients (64 +/- 12 years, 40 males) with symptomatic common atrial flutter using a novel 9 Fr 8-mm-tip catheter. BCB in the CTI 30 minutes following the final cryoapplication was the ablation endpoint. Thirty days post ablation, persistence of BCB was controlled by repeat electrophysiological study (EPS). RESULTS: In all patients BCB was achieved with a mean of 9 (IQR 7-17.5) cryo applications and a mean cryo time of 2,378 seconds (IQR 1,680-3,474 seconds). In 5 of 50 patients, common atrial flutter recurred within 1 month post cryoablation. In 30 of 32 recurrence-free patients, persistence of BCB was verified. In 2 patients, resumption of isthmus conduction was detectable. Including relapses, 81.1% of patients (30/37) showed persistence of BCB. No patients reported pain during cryoapplication. No procedural complications were observed. CONCLUSIONS: Cryoablation of the CTI using a large-tip catheter is feasible and safe in the treatment of common atrial flutter. Acute and short-term success rates are comparable to those reported for radiofrequency (RF) ablation. Besides short-term clinical success, the persistence of BCB demonstrates efficacy of the cryoablation technique.

Adult↗

Implementation of reperfusion therapy in acute myocardial infarction. A policy statement from the European Society of Cardiology.

Reperfusion therapy in ST-segment elevation myocardial infarction (STEMI) is the most important component of treatment, as it strongly influences short- and long-term patient outcome. The main objective of healthcare providers should be to achieve at least 75% of reperfusion therapy applied to patients suffering from STEMI in a timely manner, and preferably within the first 3 h after onset of symptoms. Establishing networks of reperfusion at regional and national level, implying close collaboration between all the actors involved in reperfusion therapy, namely hospitals, departments of cardiology, PCI centres, emergency medical systems (EMS), (para)medically staffed ambulances, private cardiologists, primary care physicians, etc., is a key issue. All forms of reperfusion, depending on local facilities, need to be available to patients. Protocols must be written and agreed for the strategy of reperfusion to be applied within a network. Early diagnosis of STEMI is essential and is best achieved by rapid ECG recording and interpretation at first medical contact, wherever this contact takes place (hospital or ambulance). Tele-transmission of ECG for immediate interpretation by experienced cardiologists is an alternative. Primary PCI is the preferred reperfusion option if it can be performed by experienced staff within 90 min after first medical contact. Thrombolytic treatment, administered if possible in the pre-hospital setting, is a valid option if PCI cannot be performed in a timely manner, particularly within the first 3 h following onset of symptoms. Thrombolysis is not the end of the reperfusion therapy. Rescue PCI must be performed in the case of thrombolysis failure. Next-day PCI after successful thrombolysis has been proven efficacious. Quality control is important for monitoring the efficacy of networks of reperfusion. All elements that influence time to reperfusion must be taken into account, particularly transfer delays, in-hospital delays, and door-to-balloon or door-to-needle times. The rate of reperfusion achieved must also be taken into consideration. Professional organizations such as the European Society of Cardiology (ESC) have the responsibility to impart this message to the cardiology community, and inform politicians and health authorities about the best possible strategy to achieve reperfusion therapy.

Angioplasty, Balloon, Coronary↗

Diagnostic utility of new immunoassays for the cardiac markers cTnI, myoglobin and CK-MB mass.

OBJECTIVES: We investigated the diagnostic value of a new system, the Innotrac Aio! immunoassays for troponin, myoglobin and CK-MB, in 270 samples from patients with ACS, after bypass surgery (CABG) or with stable heart failure in comparison to the respective Roche assays. RESULTS: The values of the cardiac markers assessed by the respective assays correlated (cTnT/cTnI Rho = 0.94, myoglobin Rho = 0.87, CK-MB Rho = 0.84). If values were dichotomised, we found a high concordance of test positive and negative classified patients by troponins with the respective assays. CONCLUSION: There is strong evidence that the Innotrac Aio! system for cTnI measurement can be used reliably.

Acute Disease↗

Relation of N-terminal pro B-type natriuretic peptide to progression of aortic valve disease.

AIMS: Recently an elevation of B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) in patients with aortic stenosis (AS) and aortic regurgitation (AR) has been described. The objective of this study was to evaluate the relation of NT-proBNP values to the progression of aortic valve disease. METHODS AND RESULTS: One hundred and sixty-eight patients were included. NT-proBNP was elevated in patients with AS (n=109) and AR (n=37) linked to disease severity. Values for NT-proBNP, pressure gradient, and left ventricular mass were identical in patients (n=22) after previous valve replacement and in those patients with mild AS. NT-proBNP levels decreased in 86 patients after valve replacement (2292+/-353 vs. 785+/-101 pg/ml; P<0.01) but increased in 82 patients who were treated conservatively (616+/-120 vs. 1155+/-432 pg/mL; P=0.029), related to the progression of disease. CONCLUSION: NT-proBNP is elevated in patients with aortic valve disease linked to disease severity and decreases after successful surgical therapy but increases in conservatively treated patients. These data underline the consistent relation of NT-proBNP to severity of aortic valve disease. Therefore, NT-proBNP should be considered as a biomarker for the monitoring of disease during follow-up, but further studies are warranted.

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Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology.

In patients with stable CAD, PCI can be considered a valuable initial mode of revascularization in all patients with objective large ischaemia in the presence of almost every lesion subset, with only one exception: chronic total occlusions that cannot be crossed. In early studies, there was a small survival advantage with CABG surgery compared with PCI without stenting. The addition of stents and newer adjunctive medications improved the outcome for PCI. The decision to recommend PCI or CABG surgery will be guided by technical improvements in cardiology or surgery, local expertise, and patients' preference. However, until proved otherwise, PCI should be used only with reservation in diabetics with multi-vessel disease and in patients with unprotected left main stenosis. The use of drug-eluting stents might change this situation. Patients presenting with NSTE-ACS (UA or NSTEMI) have to be stratified first for their risk of acute thrombotic complications. A clear benefit from early angiography (<48 h) and, when needed, PCI or CABG surgery has been reported only in the high-risk groups. Deferral of intervention does not improve outcome. Routine stenting is recommended on the basis of the predictability of the result and its immediate safety. In patients with STEMI, primary PCI should be the treatment of choice in patients presenting in a hospital with PCI facility and an experienced team. Patients with contra-indications to thrombolysis should be immediately transferred for primary PCI, because this might be their only chance for quickly opening the coronary artery. In cardiogenic shock, emergency PCI for complete revascularization may be life-saving and should be considered at an early stage. Compared with thrombolysis, randomized trials that transferred the patients for primary PCI to a 'heart attack centre' observed a better clinical outcome, despite transport times leading to a significantly longer delay between randomization and start of the treatment. The superiority of primary PCI over thrombolysis seems to be especially clinically relevant for the time interval between 3 and 12 h after onset of chest pain or other symptoms on the basis of its superior preservation of myocardium. Furthermore, with increasing time to presentation, major-adverse-cardiac-event rates increase after thrombolysis, but appear to remain relatively stable after primary PCI. Within the first 3 h after onset of chest pain or other symptoms, both reperfusion strategies seem equally effective in reducing infarct size and mortality. Therefore, thrombolysis is still a viable alternative to primary PCI, if it can be delivered within 3 h after onset of chest pain or other symptoms. Primary PCI compared with thrombolysis significantly reduced stroke. Overall, we prefer primary PCI over thrombolysis in the first 3 h of chest pain to prevent stroke, and in patients presenting 3-12 h after the onset of chest pain, to salvage myocardium and also to prevent stroke. At the moment, there is no evidence to recommend facilitated PCI. Rescue PCI is recommended, if thrombolysis failed within 45-60 min after starting the administration. After successful thrombolysis, the use of routine coronary angiography within 24 h and PCI, if applicable, is recommended even in asymptomatic patients without demonstrable ischaemia to improve patients' outcome. If a PCI centre is not available within 24 h, patients who have received successful thrombolysis with evidence of spontaneous or inducible ischaemia before discharge should be referred to coronary angiography and revascularized accordingly--independent of 'maximal' medical therapy.

Angioplasty, Balloon, Coronary↗

Determination of arterial compliance using blood pressure waveform analysis with the CR-2000 system: Reliability, repeatability, and establishment of normal values for healthy European population--the seven European sites study (SESS).

BACKGROUND: We determined the reliability and repeatability of measurements of arterial compliance (AC) and gender- and age-specific normal ranges for a healthy European population. METHODS: Three hundred eight healthy volunteers from seven sites were evaluated. Two measurements were taken during the first visit, repeated on a second visit 1 to 4 weeks later. We used the HDI/PulseWave CR-2000 for measurements of AC. RESULTS: Intravisit measurements, taken 5 min apart, differed by less than 3% (range, 0.36% to 2.97%). All intervisit measures differed by less than 4% (range, 0.24% to 3.67%); none of these differences was statistically significant. All correlation coefficients for pairs of AC parameters measured 5 min apart at the same visit were significant at P < .0001. Paired AC parameters at visit 1 and 2 were highly correlated (P < .0001). Repeated measures GLM (general linear model) failed to detect a significant association between either of the AC parameters and visit (first or second), time (first or second measure at the same visit), and visit-by-time (the interaction of the two preceding factors), suggesting that order of measure had no effect on the final value. Analysis of reliability was used to develop a strictly parallel model estimate of unbiased reliability. Both intravisit and intervisit estimates of reliability indicate good repeatability of measure and were significant (P < .0001). The AC values were found to differ significantly by age group, with an inverse association between each of the AC parameters and age group. CONCLUSIONS: Measurement of the arterial waveform with the CR-2000 system is highly reproducible in healthy subjects.

Adolescent↗

Usefulness of atrial fibrillation burden as a predictor for success of pulmonary vein isolation.

BACKGROUND: The definition of symptomatic improvement after pulmonary vein isolation (PVI) is controversial. We assessed primarily the usefulness and predictive accuracy (PA) of AF (atrial fibrillation) burden (AFB) within the first 3 months after the procedure as an early predictor for curative success as well as reduction of symptoms. METHODS: We studied 100 pts (62 men, mean age: 54 +/- 9 years, LVEF: 57 +/- 9%, paroxysmal AF, 85, persistent AF, 15) who underwent PVI. RF ablation was used in 63 patients. The combination of cryoablation and RF (Hybrid therapy) was used in the remaining 37 patients, in 19 patients of whom additionally linear lesions were performed. All patients were followed up 3 months after PVI (the blanking period) and every 3 months thereafter. The significance of early recurrence of AF (ERAF) was separately analyzed for RF and for hybrid therapy arm. Quality of life (QoL) was assessed using the physical composite summary score (PCS) and mental composite summary score (MCS). AFB was dichotomized at: 0, 0.5, 1, 6, 12, and 24 hours. RESULTS: ANOVA revealed significant differences between PCS at baseline and after PVI in patients without recurrence and with those with postablation AFB <12 hours. There was no difference between PCS in patients with AFB > or =12 hours within a 3 months interval and PCS at baseline. ERAF occurred in 35% of patients (16 patients, AFB > or =12 hours). Symptomatic ERAF occurred in 29 patients (17 patients AFB > or =12 hours). After the blanking period, documented AF recurrence was found in 50 patients (17 patients, AFB > or =12 hour). Symptomatic late recurrence was found in 47 patients (31 patients with AFB > or =12 hours). Absence of ERAF was revealed to be predictive for long-term success and symptomatic ERAF was found to be predictive for symptomatic AF recurrence (P <0.0001). CONCLUSION: AF recurrence with AFB > or =12 hours within 3 months is associated with a missed improvement of QoL. Symptomatic ERAF predicts recurrence independently of therapy.

Analysis of Variance↗

Engineering and medical applications of diatoms.

Biologists, and diatomists in particular, have long studied the properties of single-cell algae, and engineers are just discovering how to exploit features unique to these organisms. Their uniform nanopore structure, microchannels, chemical inertness, and silica microcrystal structure suggest many nanoscale applications. This paper proposes three potential research initiatives taking advantage of diatom morphology and mechanical and chemical properties: (1) embedding diatom frustules in a metal-film membrane; (2) magnetizing frustules for pinpoint drug delivery; and (3) producing silica nanopowders from frustules. The potential benefits of each initiative and its technical challenges are outlined.

Biomedical Engineering↗

Relation of N-terminal pro-B-type natriuretic peptide to severity of valvular aortic stenosis.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been shown to be a reliable biochemical marker for left ventricular wall stress and is increased in patients with aortic stenosis (AS). We evaluated the role of NT pro-BNP as a biochemical marker in the diagnosis of AS and whether it contributes to the optimal timing for aortic valve replacement (AVR). Included in this study were 146 patients who had AS, 31 who underwent AVR, and 32 who had "normal valve function" (controls). Increased NT pro-BNP was closely linked to severity of AS (mild AS 612 +/- 151 pg/ml, moderate AS 1,441 +/- 32 pg/ml, severe AS 2,579 +/- 13 pg/ml, AVR 593 +/- 148 pg/ml, controls 140 +/- 27 pg/ml; p <0,01) and to New York Heart Association functional class (class I 601 +/- 116 pg/ml, class II 1,119 +/- 216 pg/ml, class III 1,998 +/- 459 pg/ml, class IV 5,107 +/- 1,512 pg/ml; p <0.01). Area under the receiver-operating characteristic curve for NT pro-BNP as a predictor for AVR was 0.73. Using an optimized cutoff of 550 pg/ml for NT-proBNP, the positive predictive value was 85%. Thus, NT pro-BNP is linked to severity of AS and New York Heart Association class and is an indication for AVR. Therefore, it is a useful biochemical marker to evaluate severity of AS, monitor disease progression at an early stage, and decide on the optimal time for AVR.

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